Hwang Deok-Sang, Gu Pil Sung, Kim Namkwon, Jang Young Pyo, Oh Myung Sook
Department of Oriental Gynecology, College of Oriental Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
Department of Life and Nanopharmaceutical Sciences, Graduate school, Kyung Hee University, Seoul, 02447, Republic of Korea.
Environ Toxicol. 2018 Jan;33(1):23-31. doi: 10.1002/tox.22463. Epub 2017 Oct 6.
Neuroinflammation plays a critical role in the pathogenesis of degenerative brain diseases such as Alzheimer's disease and Parkinson's disease. Microglia are the major components of the brain immune system that regulate inflammatory processes. Activated microglia release pro-inflammatory factors and cytokines, resulting in neuronal cell death. We focused on inhibiting the activation of microglia from a stimulus as a strategy to search for neuroprotective drugs. Rhei Undulati Rhizoma (RUR) is traditionally used to treat various inflammatory disorders. In this study, we investigated whether RUR modulates inflammatory processes in lipopolysaccharide (LPS)-stimulated BV2 microglia cells and the mouse brain. RUR exerted anti-neuroinflammatory effects by inhibiting the production of nitric oxide and reactive oxygen species induced by LPS via the downregulation of transcription factors such as inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) without causing cytotoxicity. RUR also regulated mitogen-activated protein kinase pathway by inhibiting phosphorylation of p38 and c-Jun N-terminal kinases and translocation of nuclear factor kappa B. Moreover, RUR attenuated LPS-induced glial activation and COX-2 expression in the substantia nigra and hippocampus of the mouse brain. These results indicate that RUR is a potential candidate to treat neurodegenerative diseases by regulating neuroinflammation.
神经炎症在诸如阿尔茨海默病和帕金森病等退行性脑疾病的发病机制中起着关键作用。小胶质细胞是调节炎症过程的脑免疫系统的主要组成部分。活化的小胶质细胞释放促炎因子和细胞因子，导致神经元细胞死亡。我们专注于从刺激源抑制小胶质细胞的活化，以此作为寻找神经保护药物的一种策略。大黄（Rhei Undulati Rhizoma，RUR）传统上用于治疗各种炎症性疾病。在本研究中，我们调查了RUR是否能调节脂多糖（LPS）刺激的BV2小胶质细胞和小鼠脑中的炎症过程。RUR通过下调转录因子如诱导型一氧化氮合酶和环氧化酶-2（COX-2）来抑制LPS诱导的一氧化氮和活性氧的产生，从而发挥抗神经炎症作用，且不会引起细胞毒性。RUR还通过抑制p38和c-Jun氨基末端激酶的磷酸化以及核因子κB的转位来调节丝裂原活化蛋白激酶途径。此外，RUR减轻了小鼠脑黑质和海马中LPS诱导的胶质细胞活化和COX-2表达。这些结果表明，RUR可能是一种通过调节神经炎症来治疗神经退行性疾病的潜在候选药物。
